Year: 2006
Type: article
Abstract: Human neuroblastoma I-type cells have been proposed as a population of malignant neural crest stem cells, based on their high tumorigenic activity, expression of stem cell markers, and ability to differentiate to cells of neural crest lineages, including neuroblastic (N-type) and myoblastic/glial /melanocytic (S-type) cells. My findings demonstrated that some of the I-type cells were cancer stem cells with self-renewal capacity and multipotent differentiation potential, and CD24 was a neuroblatoma stem cell-related marker and could be used to enrich cancer stem cells in the BE(2)-C I-type cell line by cell sorting. This study also showed that expression of neuroblastoma stem cell activities required the polycomb family transcriptional repressor Bmi-1. Bmi-1 expression levels were found to exert an “instructive” influence on lineage commitment by the I-type cells. Differentiation of I-type cells to S-type cells was accompanied by a marked decrease in Bmi-1 expression, and experimental downregulation of Bmi-1 in I- type cells was found to promote their differentiation along the Schwann/glial (S-type) pathway. In contrast, N-type cells derived from I-type cells expressed higher levels of Bmi-1, and experimental upregulation of Bmi-1 was found to induce the I-type cells to differentiate along the neuronal (N-type) pathway. Thus, the results of this study identified the existence of a complex mechanism in these cells that was dependent upon the concentrations of a protein, Bmi-1, for both self-renewal property and for the outcomes of their differentiation programs.
Author: Jun Ma
Institution: University of Toledo
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1931169131